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Studying the networks of connections in the brains of people affected by schizophrenia, bipolar disease or depression has allowed Dr. Peter Williamson, from Western University, to gain a better understanding of the biological basis of these important diseases. Dr. Williamson and colleagues have shown that different networks, found specifically in humans, are disrupted in different psychiatric diseases. These results were presented at the 2013 Canadian Neuroscience Meeting, the annual meeting of the Canadian Association for Neuroscience – Association Canadienne des Neurosciences (CAN-ACN).

Previously, researchers had attempted to use genetic approaches to help explain the biological basis of neuropsychiatric diseases, but genetics can only explain a small percentage of cases. Today researchers have begun using new imaging techniques to study connections in the brains of living patients, and this approach is revealing important differences between patients suffering from schizophrenia, bipolar disorder, and depression, and persons not affected by these disorders.

Schizophrenia and bipolar disorder are uniquely human diseases. Though some animal models exist for these diseases, animals cannot experience these diseases as we do, since they lack our language capacities, and the ability to represent feelings and ideas, their own and those of others, across time. These specifically human capabilities are encoded in specifically human neural networks, such as an emotional encoding network, found to be disrupted in mood disorders, such as depression and bipolar disorder, and the directed effort network which fails in schizophrenia.

Concluding quote from Dr. Williamson: “We are not likely to understand the extremely complex interactions between the hundreds of genes and environmental events that underlie neuropsychiatric disorders in our lifetimes. The challenge of our time is to find the final common pathways of these disorders”

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MRI may be an effective way to diagnose mental illnesses such as bipolar disorder, according to experts from the Icahn School of Medicine at Mount Sinai. In a landmark study using advanced techniques, the researchers were able to correctly distinguish bipolar patients from healthy individuals based on their brain scans alone. The data are published in the journal Psychological Medicine.

Currently, most mental illnesses are diagnosed based on symptoms only, creating an urgent need for new approaches to diagnosis. In bipolar disorder, there may be a significant delay in diagnosis due to the complex clinical presentation of the illness. In this study, Sophia Frangou, MD, Professor of Psychiatry and Chief of the Psychosis Research Program at the Ichan School of Medicine at Mount Sinai teamed up with Andy Simmons, MD, of the Kings College London and Janaina Mourao-Miranda, MD, of University College London, to explore whether brain imaging could help correctly identify patients with bipolar disorder.

“Bipolar disorder affects patients’ ability to regulate their emotions successfully, which puts them at great disadvantage in their lives,” said Dr. Frangou. “The situation is made worse by unacceptably long delays, sometimes of up to 10 years, in making the correct diagnosis. Bipolar disorder may be easily misdiagnosed for other disorders, such as depression or schizophrenia. This is why bipolar disorder ranks among the top ten disorders causing significant disability worldwide.”

Dr. Frangou and her team used MRI to scan the brains of people with bipolar disorder and of healthy individuals. Using advanced computational models, they were successful in correctly separating people with bipolar disorder from healthy individuals with 73 percent accuracy using their brain imaging scans alone. They replicated their finding in a separate group of patients and healthy individuals and found a 72 percent accuracy rate.

Dr. Simmons added, “The level of accuracy we achieved is comparable to that of many other tests used in medicine. Additionally, brain scanning is very acceptable to patients as most people consider it a routine diagnostic test.”

“This approach does not undermine the importance of rigorous clinical assessment and the importance of building relationships with patients but provides biological justification for the type of diagnosis made,” said Dr. Frangou. “However, diagnostic imaging for psychiatry is still under investigation and not ready for widespread use. Nonetheless, our results together with those from other labs are a harbinger of a major shift in the way we approach diagnosis in psychiatry.”

Dr. Frangou recently joined Mount Sinai as Chief of the Psychosis Research Program in the Division of Psychiatric Genomics in the Department of Psychiatry at Mount Sinai. A leading authority on neuroimaging in schizophrenia and bipolar disorder, Dr. Frangou was recruited to Mount Sinai to establish a clinical and translational psychosis program. By building on Mount Sinai’s strengths in clinical investigation, the program aims to translate research in genetics, neuroimaging, and neurobiology into clinical trials and clinical care.

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Research from North Carolina State University, the Research Triangle Institute (RTI) and the University of South Florida shows that outpatient treatment of mental illness significantly reduces arrest rates for people with mental health problems and saves taxpayers money.

“This study shows that providing mental health care is not only in the best interest of people with mental illness, but in the best interests of society,” says Dr. Sarah Desmarais, an assistant professor of psychology at NC State and co-author of a paper describing the research.

The researchers wanted to determine the extent to which treating mental illness can keep people with mental health problems out of trouble with the law. It is well established that people with mental health problems, such as schizophrenia or bipolar disorder, make up a disproportionate percentage of defendants, inmates and others who come into contact with the criminal justice system.

The researchers identified 4,056 people who had been hospitalized for mental illness in 2004 or 2005 and then tracked them from 2005 to 2012. The researchers were able to determine which individuals were receiving government-subsidized medication and which were receiving government-subsidized outpatient services, such as therapy. The researchers were also able to determine who was arrested during the seven-year study period.

“Our research shows that people receiving medication were significantly less likely to be arrested,” Desmarais says. “Outpatient services also resulted in a decreased likelihood of arrest.”

The researchers also compared criminal justice costs with mental health treatment costs. Individuals who were arrested received less treatment and each cost the government approximately $95,000 during the study period. Individuals who were not arrested received more treatment and each cost the government approximately $68,000 during the study period.

“It costs about $10 less per day to provide treatment and prevent crime. That’s a good investment,” Desmarais says.

“Effects of Outpatient Treatment on Risk of Arrest of Adults With Serious Mental Illness and Associated Costs”

Abstract: Objective: This study examined whether possession of psychotropic medication and receipt of outpatient services reduce the likelihood of posthospitalization arrest among adults with serious mental illness. A secondary aim was to compare service system costs for individuals who were involved with the justice system and those who were not. Methods: Claims data for prescriptions and treatments were used to describe patterns and costs of outpatient services between 2005 and 2012 for 4,056 adult Florida Medicaid enrollees with schizophrenia or bipolar disorder after discharge from an index hospitalization. Multivariable time-series analysis tested the effects of medication and outpatient services on arrest (any, felony, or misdemeanor) in subsequent 30-day periods. Results: A total of 1,263 participants (31%) were arrested at least once during follow-up. Monthly medication possession and receipt of outpatient services reduced the likelihood of any arrests (misdemeanor or felony) and of misdemeanor arrests. Possession of medications for 90 days after hospital discharge also reduced the likelihood of arrest. Prior justice involvement, minority racial-ethnic status, and male sex increased the risk of arrest, whereas older age decreased it. Criminal justice and behavioral health system costs were significantly higher for the justice-involved group than for the group with no justice involvement. Conclusions: Routine outpatient treatment, including medication and outpatient services, may reduce the likelihood of arrest among adults with serious mental illness. Medication possession over a 90-day period after hospitalization appears to confer additional protection. Overall, costs were lower for those who were not arrested, even when they used more outpatient services.

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Researchers have discovered a pathway by which the brain controls a molecule critical to forming long-term memories and connected with bipolar disorder and schizophrenia.

The discovery was made by a team of scientists led by Alexei Morozov, an assistant professor at the Virginia Tech Carilion Research Institute.

The mechanism – a protein called Rap1 – controls L-type calcium channels, which participate in the formation of long-term memories. Previous studies have also linked alterations in these ion channels to certain psychiatric disorders. The discovery of the channels’ regulation by Rap1 could help scientists understand the physiological genesis of bipolar disorder and schizophrenia.

“People with genetic mutations affecting L-type calcium channels have higher rates of bipolar disorder and schizophrenia,” said Morozov. “This suggests that there might be a relationship between the activation of L-type calcium channels and these psychiatric disorders. Understanding how these ion channels are controlled is the first step to determining how their functioning or malfunctioning affects mental health.”

A single neuron in the brain can have thousands of synapses, each of which can grow, strengthen, weaken, and change structurally in response to learning new information. Electric signals traveling from neuron to neuron jump across these synapses through chemical neurotransmitters. The release of these chemicals is caused by the flow of electrically charged atoms through a particular subset of ion channels known as voltage-gated calcium channels.

Previous studies have shown that blocking these ion channels inhibits the formation of long-term memories. Although it was known that L-type calcium channels are activated in response to learning, how they are controlled was a mystery.

In the experiment, Morozov and colleagues knocked out the gene responsible for coding the enzyme Rap1, which he suspected played a role in activating L-type calcium channels. The researchers then used live imaging techniques to monitor the release of neurotransmitters and electron microscopy to visualize L-type channels at synapses. They discovered that, without Rap1, the L-type calcium channels were more active and more abundant at synapses all the time, increasing the release of neurotransmitters. The results showed that Rap1 is responsible for suppressing L-type calcium channels, allowing them to activate only at the proper moments, possibly during long-term memory formation.

“Our next step is to determine whether this new signaling pathway is altered in cases of mental disease,” said Morozov. “If so, it could help us gain a better understanding of the molecular underpinnings of channel-related psychiatric disorders, such as bipolar disorder and schizophrenia. Such knowledge would go a long way toward developing new therapeutic methods.”

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Lithium can reduce suicide risk and help prevent deliberate self harm in people with mood disorders, according a new study in British Medical Journal (BMJ).

The research showed that the drug appeared to lower the likelihood of death and suicide by over 60% compared with placebo.

The finding “reinforces lithium as an effective agent to reduce the risk of suicide in people with mood disorders,” the scientists said.

Mood disorders are a major cause of global disability – the two main types are unipolar, which is commonly known as clinical depression, and bipolar disorder, which can also be called manic depression.

Both conditions are severe and long-term and involve extreme mood swings. Patients with bipolar disorder, however, also experience episodes of mania or hypomania.

People affected by a mood disorder have a 30 times higher likelihood of suicide than the general population. Mood stabilizing drugs, such as lithium, anticonvulsants or antipsychotics, used for the treatment of these conditions can help keep mood within normal limits.

However, experts have not known their role in suicide prevention, and therefore, researchers from the universities of Oxford, UK and Verona, Italy set out to examine whether lithium has a particular preventive effect for suicide and self harm in patients with unipolar and bipolar mood disorders.

Forty-eight randomized controlled trials consisting of 6,674 volunteers were examined. The studies compared lithium with either placebo or active drugs in long-term treatment for mood disorders.

Results showed that lithium was more successful than placebo in lowering the number of suicides and deaths from any cause.

However, no clear benefits were found for lithium in preventing deliberate self harm compared with placebo.

The experts said:

“When lithium was compared with each active individual treatment, a statistically significant difference was found only with carbamazepine for deliberate self harm. Overall, lithium tended to be generally better than the other active treatments, with small statistical variation between the results.”

“This updated systematic review reinforces lithium as an effective agent to reduce the risk of suicide in people with mood disorders,” explained the investigators.

The drug’s anti-suicidal effects may be exerted by “reducing relapse of mood disorder,” the authors said.

However, they pointed out “there is some evidence that lithium decreases aggression and possibly impulsivity, which might be another mechanism mediating the anti-suicidal effect.”

Lithium has many side effects, the scientists pointed out. However, doctors “need to take a balanced view of the likely benefits and harm of lithium in the individual patient.”

The authors concluded:

“Understanding the mechanism by which lithium acts to decrease suicidal behavior could lead to a better understanding of the neurobiology of suicide.”

A 2009 study suggested that very low levels of lithium in drinking water may help prevent suicide in the general population.

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New Northwestern Medicine® research offers one of the first in-depth studies of how physiological changes during pregnancy reduce the effects of a commonly used drug to treat bipolar disorder, making women more vulnerable to recurring episodes. The new findings will help psychiatrists and physicians prevent bipolar manic and depressive symptoms during pregnancy, which are risky for the health of the mother and her unborn child.

When a woman with bipolar disorder becomes pregnant, she and her physician often don’t realize her medication needs adjusting to prevent the symptoms from coming back – a higher risk during pregnancy. There also is little information and research to guide dosing for psychiatric medications during pregnancy.

Approximately 4.4 million women in the U.S. have bipolar disorder with women of childbearing age having the highest prevalence.

The new study shows the blood concentration of the commonly used drug lamotrigine decreases in pregnant women. About half of the women in the study had worsening depressive symptoms as their lamotrigine blood levels dropped. The drug levels fall because women have increased metabolism during pregnancy.

“Now physicians change the dose of the drug in response to women’s symptoms worsening,” said lead investigator Crystal Clark, M.D., an assistant professor of psychiatry and behavioral sciences at Northwestern University Feinberg School of Medicine and a psychiatrist at Northwestern Memorial Hospital. “We need to optimize their medication dosing so they stay well.”

The study results will help physicians understand how to increase their patients’ doses during pregnancy and then reduce them postpartum to avoid toxicity, Clark said. Guidelines for prescribing the drug for pregnant women with the disorder also are included.

The study was published in the American Journal of Psychiatry.

Depressive episodes — as opposed to manic — are most likely to recur in pregnant women with bipolar disorder.

“The safety of the fetus is at risk,” Clark said. “Pregnant women that are depressed are less likely to take care of themselves which often leads to poor nutrition, lack of compliance with prenatal care and isolation from family and friends. It has also been linked to premature births and babies with low birth weights among other poor birth outcomes.”

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Although older adults with serious mental illness didn’t have more recorded physical illness and had fewer outpatient visits to primary care physicians, they made more medical emergency department visits and had considerably longer medical hospitalizations than older adults without mental illness according to a study conducted by researchers from the Regenstrief Institute and the Indiana University Center for Aging Research.

“Our comparison of health care utilization between seriously mentally ill patients and age-matched primary-care patients provides critical data for the physicians, health care systems and policy makers who will be caring for the growing number of older adults, many of whom have mental illness,” said Regenstrief Institute investigator Hugh C. Hendrie, M.B., Ch.B., D.Sc., Indiana University Center for Aging Research center scientist and professor of psychiatry at the IU School of Medicine. Dr. Hendrie, who is a geriatric psychiatrist and health services researcher, is the first author of the study.

The study, “Comorbidity Profile and Healthcare Utilization in Elderly Patients With Serious Mental Illnesses,” is published in the December issue of The American Journal of Geriatric Psychiatry.

A 2012 report from the Institute of Medicine estimated that as many of one in five older adults have one or more mental health conditions or problems stemming from substance misuse or abuse. The IOM report authors included Regenstrief Institute investigator Christopher Callahan, M.D., Cornelius and Yvonne Pettinga Professor of Medicine at the IU School of Medicine who is also a co-author of the new study. Dr. Callahan is founding director of the IU Center for Aging Research.

The American Journal of Geriatric Psychiatry study notes, “The increased likelihood of falls together with the significantly greater number of emergency department visits and length of hospitalization also suggest that those with severe mental illness represent a vulnerable elderly population that deserve more intensive studies, leading hopefully to a better integrated model of medical and psychiatric care including consideration of psychosocial factors.”

Individuals with severe mental illness in the study were patients of Eskenazi Health Midtown Community Mental Health. The patients had severe chronic depression (48 percent), schizophrenia (39 percent) and bipolar disorder (14 percent). Others in the study were patients from Wishard-Eskenazi primary care sites.

“This study highlights a major challenge faced by older adults with severe mental illnesses and the increased burden it places on our health care system,” said Julie L. Szempruch, RN, CNS, associate vice president of Eskenazi Health Midtown Community Mental Health.

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A new study published in the British Medical Journal finds a small but significant increase in psychosis risk for people who suffer the loss of a family member in childhood.

Although we know that adult health can be influenced by the genes we inherit from our parents, as well as the environment and lifestyle we experience as children, some evidence has suggested that psychological stress from the mother can also affect the development of a fetus.

But previous studies examining a link between a mother’s psychological stress and her offspring’s mental health have not been very conclusive.

This new study wanted to test this link further by seeing if children born to mothers who went through severe bereavement before, during or after pregnancy would be more likely to show symptoms of psychosis in adulthood.

The study was a large systematic review analyzing the medical records of 946,994 people born between 1973 and 1985 in Sweden.

The researchers identified mothers who had experienced the death of their parents, offspring or father of their children in a period between 6 months before conceiving and up to 13 years after giving birth. They also took into account the cause of death when bereavements had occurred in these families.

Overall, 321,249 (33%) of the children in the study experienced a family death before the age of 13.

‘No link’ between grieving during pregnancy and offspring mental health

The researchers found that 1,323 (0.4%) of these children later developed a delusional or “non-affective” psychosis (such as schizophrenia), while 556 (0.17%) of these children went on to develop an emotional disorder or “affective” psychosis (such as bipolar disorder).

By looking at when the bereavements occurred, the study concluded that mothers who suffered a bereavement before or during their pregnancy were not more likely than usual to have children who would develop psychosis.

So, it could not be proved that the psychological stress of a grieving mother can affect the future mental health of her fetus.

Dr. Kathryn Abel, lead author of the study, told Medical News Today that, despite previous studies suggesting the contrary, she was not surprised by their results:

“Previous findings relating to risk of schizophrenia or other illnesses have not been very strong and often were only seen in particular groups, such as those without a history of psychosis already in the family, or only in men.”

But the researchers did measure a small increased risk of people developing psychosis who had experienced the death of a family member in their childhood.

The study found that this risk increased in people who had lost a loved one from suicide (rather than from natural causes), and the risk also increased the earlier in childhood that this death occurred.

How reliable are the results?

woman with bipolar disorder
Of the bereaved children, 0.17% went on to develop an “affective” psychosis, such as bipolar disorder.

Although the study could identify when and how bereavements had occurred in these families, it is difficult to measure the level of psychological stress experienced by the families in the study.

Some families may have grieved for a long time, and some may have grieved comparatively little – for example, if the death was of an elderly relative who had been ill for some time – in which case, their passing may have provided some relief for the family. So some aspects of the study’s results may be subjective.

There are also a lot of other contributing childhood factors that can contribute to whether a person is more at risk of psychosis. These include socioeconomic status, neglect, abuse and bullying. These factors could also have had an effect on the results that was difficult to measure.

Also, the study only examined how experiencing a family death in childhood affects people born in Sweden. The researchers believe that further research needs to be done in non-Western and ethnically diverse populations to give us an overall picture of how grief might affect psychological development.

Dr. Abel told Medical News Today that it is possible “in non-Western populations, some societies might provide more support to bereaved families, or manage death and bereavement across society so it is less stressful and has less broad consequences on childhood.”

But Dr. Abel also mentioned that, in some societies, the opposite could be true, and “differences between risk of psychosis in those exposed and unexposed [to bereavement in childhood] could be greater.”

The researchers hope that having a better understanding of the childhood factors influencing risk of adult psychosis will ensure that “appropriately timed and appropriately resourced interventions can be developed to protect vulnerable families and children.”

Written by David McNamee

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How does an animal recognize another of the same species? Researchers from the Columbia University Medical Center in New York say they have uncovered the brain region responsible for this process – known as social memory.

The research team says their findings could assist in the understanding and treatment of disorders associated with altered social behaviors, including autism, schizophrenia and bipolar disorder.

The hippocampus is an area of the brain that is known to be associated with memory.

According to the researchers, recent studies have shown there are subregions in the hippocampus that have different responsibilities.

They note that the dentate gyrus subregion allows us to distinguish between different environments, the CA3 subregion enables us to recall memories from partial cues, and the CA1 subregion plays an important role in all areas of memory.

But there is another subregion in the hippocampus between CA3 and CA1, called CA2. Until now, scientists have been unclear on what role this subregion plays in memory.

Inactivated CA2 region led to a lack of social memory

To find out, the researchers were able to selectively block CA2 neurons in the adult offspring of a transgenic mouse.

mouse
Researchers found that mice with an inactivated CA2 region in the brain lacked social memory.

These mice were then subject to a series of behavioral experiments. When it came to social memory, the researchers found that the mice were displaying interesting behavior.

“Normally, mice are naturally curious about a mouse they’ve never met; they spend more time investigating an unfamiliar mouse than a familiar one,” explains first author Dr. Frederick L. Hitti.

“In our experiment, however, mice with an inactivated CA2 region showed no preference for a novel mouse versus a previously encountered mouse, indicating a lack of social memory.”

On conducting two other experiments in the CA2-deficient mice, which tested how they recognized new objects through vision and smell, the researchers found the mice acted normally. This indicates that the CA2 subregion may be solely responsible for social memory.

CA2 potential new target for treatment of social disorders

The investigators say these findings may have important implications for behavioral disorders, such as autism, schizophrenia and bipolar disorder, since these conditions are associated with impaired social memory.

They say previous studies have shown that people with schizophrenia and bipolar disorder have less active CA2 neurons, compared with healthy individuals.

Furthermore, research has shown that people with autism have impaired signaling of vasopressin – a hormone that is thought to play a role in social behavior.

Prof. Steven A. Siegelbaum, senior author of the study, says:

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Columbia University Medical Center (CUMC) researchers have determined that a small region of the hippocampus known as CA2 is essential for social memory, the ability of an animal to recognize another of the same species. A better grasp of the function of CA2 could prove useful in understanding and treating disorders characterized by altered social behaviors, such as autism, schizophrenia, and bipolar disorder. The findings, made in mice, were published today in the online edition of Nature.

Scientists have long understood that the hippocampus – a pair of seahorse-shaped structures in the brain’s temporal lobes – plays a critical role in our ability to remember the who, what, where, and when of our daily lives. Recent studies have shown that different subregions of the hippocampus have different functions. For instance, the dentate gyrus is critical for distinguishing between similar environments, while CA3 enables us to recall a memory from partial cues (e.g., Proust’s famous madeleine). The CA1 region is critical for all forms of memory.

“However, the role of CA2, a relatively small region of the hippocampus sandwiched between CA3 and CA1, has remained largely unknown,” said senior author Steven A. Siegelbaum, PhD, professor of neuroscience and pharmacology, chair of the Department of Neuroscience, a member of the Mortimer B. Zuckerman Mind Brain Behavior Institute and Kavli Institute for Brain Science, and a Howard Hughes Medical Institute Investigator. A few studies have suggested that CA2 might be involved in social memory, as this region has a high level of expression of a receptor for vasopressin, a hormone linked to sexual motivation, bonding, and other social behaviors.

To learn more about this part of the hippocampus, the researchers created a transgenic mouse in which CA2 neurons could be selectively inhibited in adult animals. Once the neurons were inhibited, the mice were given a series of behavioral tests. “The mice looked quite normal until we looked at social memory,” said first author Frederick L. Hitti, an MD-PhD student in Dr. Siegelbaum’s laboratory, who developed the transgenic mouse. “Normally, mice are naturally curious about a mouse they’ve never met; they spend more time investigating an unfamiliar mouse than a familiar one. In our experiment, however, mice with an inactivated CA2 region showed no preference for a novel mouse versus a previously encountered mouse, indicating a lack of social memory.”

In two separate novel-object recognition tests, the CA2-deficient mice showed a normal preference for an object they had not previously encountered, showing that the mice did not have a global lack of interest in novelty. In another experiment, the researchers tested whether the animals’ inability to form social memories might have to do with deficits in olfaction (sense of smell), which is crucial for normal social interaction. However, the mice showed no loss in ability to discriminate social or non-social odors.

In humans, the importance of the hippocampus for social memory was famously illustrated by the case of Henry Molaison, who had much of his hippocampus removed by surgeons in 1953 in an attempt to cure severe epilepsy. Molaison (often referred to as HM in the scientific literature) was subsequently unable to form new memories of people. Scientists have observed that lesions limited to the hippocampus also impair social memory in both rodents and humans.

“Because several neuropsychiatric disorders are associated with altered social behaviors, our findings raise the possibility that CA2 dysfunction may contribute to these behavioral changes,” said Dr. Siegelbaum. This possibility is supported by findings of a decreased number of CA2 inhibitory neurons in individuals with schizophrenia and bipolar disorder and altered vasopressin signaling in autism. Thus, CA2 may provide a new target for therapeutic approaches to the treatment of social disorders.

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